Targeted Nanoparticles for Kidney Cancer Therapy.

摘要

The long-term objective of this proposal was to design nanotubes that would preferentially target cancer cells and surrounding endothelial cells, and then to use these materials as transducers of near-infrared radiation for laser-induced thermal therapy of kidney cancer. In the work supported by this grant, we developed carbon nanotubes designed to bind to uPAR, a surface receptor overexpressed in kidney cancers and supporting endothelium that is involved in growth, migration, proliferation, metastasis and angiogenesis. We used D5, a peptide designed in the laboratory, as the targeting ligand. We demonstrated that the D5 peptide is cytotoxic to kidney cancer cells and proliferating endothelial cells. We expressed and purified a D5-GST fusion protein, and showed that this binds to the uPAR receptor. We showed that the combination of nanotubes and near-infrared radiation is effective in inhibiting the clonegenic survival of cultured kidney cancer cells. We conjugated the D5 peptide to nanotubes, showed that this new material disperses well in aqueous media, produces heat following exposure to near-infrared radiation, and profoundly reduces the viability of kidney cancer cells. We also developed fluorinated graphene oxide as a new, more flexible carbon nanoparticle, and showed that this material is also highly effective in producing heat in response to near-infrared radiation and effectively induces cell death of kidney cancer cells. This award also supported the training of predoctoral students in experimental approaches to the use of nanomaterials in kidney cancer ablation. These students gained extensive hands-on experience, made presentations, and attended conferences to advance their training.